The general aim of this research proposal is to increase our understanding of the consequences of T cell responses to antigen. Our approach will be to perform in depth studies of two types of T dependent immune responses in which conventional antibody activity has not been causally implicated, e.g., the development of various classes of delayed type hypersensitivity as well as cytotoxic T cells. Using these assays we will address ourselves to three major goals. I. Definition of the T cell sets involved in the initiation, development and regulation of various classes of DTH responses and in the development of T cell cytotoxic activity both in vivo and in vitro. II. Determine the in vivo mechanisms by which the various T cell sets recruit and otherwise interact with the accessory inflammatory cells responsible for the characteristic swelling and in duration of DTH responses with particular attention focused on the newly recognized importance of vasoactive amine regulation of leukocyte traffic and migration. III. Determine how T cell dependent vasoactive amine release could activate or alter the activity of regulatory and effector T cells which might be exposed to these amines, in particular histamine.